Reduced uterine sensitivity to estrogen in the C56Bl/6J mouse seen with advancing maternal age may be the result of decreased concentrations of cytoplasmic estrogen receptors or to a failure of estrogen-receptor complex translocation to the nucleus. It is proposed that the cytoplasmic and nuclear estrogen receptors from uterine homogenates be extracted by differential centrifugation and quantitated by saturation analysis using 3H-estradiol. Previous studies in this strain revealed that the reduction in litter size seen by 15 months of age is not accompanied by reduced rates of ovulation or tubal transport. Uterine failure is indicated by perimplantational loss of fetuses and reduced deciduoma formation in response to mechanical trauma. Biochemical extraction of uterine homogenates revealed a reduction in de novo synthesis and concentration of RNA in response to estradiol administration to aging castrates. The concentrations of specific and non-specific receptors, the affinity of the receptor for estrogen, as well as the rates of association and dissociation of the estrogen-receptor complex in uterine tissue in immature and adult virgin mice will be determined. These data will be compared with that from old virgin mice in order to elucidate the causes of decreased sensitivity to estradiol with age in this strain. The results of the proposed study will facilitate the use of this strain as an animal model to investigate the uterine effects of chronically administered synthetic steroids and chemotherapeutic agents presently being used to treat menstrual disorders, infertility and dysplasias in the human.